Idiopathic dissection of vertebral artery.
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Adult↗
Biomedical subjects
R Fellin
Publications and source records attributed to R Fellin.
Nutritional parameters, body composition, and progression of disability in older disabled residents living in nursing homes.
BACKGROUND: The evaluation of nutritional status is one of the primary components of multidimensional geriatric assessment. We investigated the relationship between some markers of malnutrition and the modifications in functional status in a sample of older disabled residents living in nursing homes. METHODS: Ninety-eight subjects who were independent in at least two activities of daily living (ADLs) were enrolled in a 2-year longitudinal study. Anthropometric, nutritional, and metabolic parameters, as well as body composition, were measured at baseline and after 2 years. RESULTS: Deteriorating functional status (> or =2 additional lost ADLs) was associated with baseline albumin levels (Tertile 3 vs Tertile 1; odds ratio [OR] 0.16, 95% confidence interval [CI] 0.04-0.67) and subscapular skinfold thickness (Tertile 3 vs. Tertile 1; OR 0.06, 95% CI 0.006-0.50). After multivariate adjustment, the OR for increasing disability was >4 in subjects with decreasing body cell mass (BCM), compared with subjects with a stable BCM. The degree of BCM reduction was strongly related to the number of additional ADLs lost at follow-up (test for trend, p = .003). CONCLUSIONS: In a sample of older disabled nursing home residents, signs of malnutrition seem to predict further worsening in functional status. Furthermore, BCM declines proportionally to the loss in ADLs, suggesting the existence of a strong relationship between BCM loss and the progressive deterioration of functional status.
Activities of Daily Living↗
A defect in glycogen synthesis characterizes insulin resistance in hypertensive patients with type 2 diabetes.
A subgroup of patients with type 2 diabetes shows a clustering of abnormalities such as peripheral insulin resistance, hypertension, and microalbuminuria. To evaluate whether these traits reflect intrinsic disorders of cell function rather than in vivo environmental effects, we studied a group of 7 nondiabetic hypertensive subjects with an altered albumin excretion rate (AER) (HyMA+) and 3 groups of patients with type 2 diabetes: 7 with normal blood pressure and normal AER (DH-MA-), 7 with high blood pressure and normal AER (DH+MA-), and 7 with both high blood pressure and altered AER (DH+MA+). Glucose disposal was measured during an hyperinsulinemic clamp (40 mU. m(2)(-1). min(-1)) with primed deuterated [6.6 (2)H(2)] glucose infusion. In the same subjects, a skin biopsy was performed and the following parameters were investigated: glucose transport (as determined by [(3)H]2-deoxyglucose uptake); glycogen synthase activity (as determined by [(14)C] glucose incorporation from UDP-[U-(14)C] glucose into glycogen); glycogen phosphorylase activity (as measured by the incorporation of [U-(14)C]glucose 1-phosphate into glycogen); and total glycogen content. In vivo glucose disposal was significantly reduced in DH+MA- and DH+MA+, with respect to DH-MA-, HyMA+, and controls. Insulin-stimulated glucose transport was similar in the 3 groups of patients with diabetes. A significant reduction of intracellular glycogen content was observed in DH+MA- and DH+MA+ compared with DH-MA- in both basal and insulin-stimulated conditions, probably because of a major impairment of glycogen synthase activity. Glycogen phosphorylase activity did not show differences between the groups. These results suggest that (1) the combination of type 2 diabetes with hypertension and altered AER is associated with impaired insulin sensitivity, and (2) intrinsic, possibly genetic, factors may account for increased peripheral insulin resistance in hypertensive microalbuminuric patients with type 2 diabetes, pointing to the reduction of glycogen synthase activity as a shared common defect.
Albuminuria↗
ACE genotype and endothelium-dependent vasodilation of conduit arteries and forearm microcirculation in humans.
The ACE gene is a candidate gene for cardiovascular disease. Endothelial dysfunction is considered an intermediate phenotype in the pathogenesis of hypertension and atherosclerosis. We evaluated the role of ACE gene polymorphism in endothelial function of young healthy humans. We assessed ACE genotype (deletion [D]/insertion [I] polymorphism) in 92 young healthy individuals. In 88 of them, endothelium-dependent (flow-mediated) vasodilation and endothelium-independent (nitroglycerin-induced) vasodilation were measured in the common femoral artery and in the brachial (n=84) artery by echo Doppler technique. In 35 subjects, we also applied the forearm perfusion technique to quantify the responses of the forearm vascular bed to 3 increasing doses of 2 endothelium-dependent vasodilators (acetylcholine and bradykinin) and 1 endothelium-independent vasodilator (sodium nitroprusside). The D allele of the ACE gene was associated with a significant blunting (Delta approximately 26%) of endothelium-dependent vasodilation in the femoral artery (P=0.02) but not in the brachial artery (P=0.55) or in the forearm microcirculation (P=0.70 to 0.80). Endothelium-independent vasodilation was unaffected by the ACE genotype. In young healthy humans, the D allele of the ACE gene is associated with selective endothelial dysfunction of the femoral artery. It remains to be determined whether this association discloses a causal role in vascular, particularly peripheral artery, disease.
Acetylcholine↗
Lipoprotein profile in older patients with vascular dementia and Alzheimer's disease.
BACKGROUND: Some alterations of the lipoprotein profile have been associated with cerebrovascular disease. Recently, it has been suggested that cerebrovascular disease might play a role in the pathogenesis of both vascular dementia (VD) and Alzheimer's disease (AD). Nevertheless, the possible association of dyslipidemias with VD or AD is still a controversial issue. METHODS: We investigated the lipoprotein profile in 100 older patients with vascular dementia (VD; no degrees: 60) or Late Onset Alzheimer's Disease (LOAD; no degrees: 40). The patients were compared with 54 community dwelling non-demented older controls. RESULTS: After adjustment for functional status, blood sedimentation rate, and serum albumin levels, no differences in lipoprotein profile emerged between the three groups, with the exception of HDL-C that was lower in VD compared with controls. Low HDL-C (< 45 mg/dL) was associated with VD (O.R.: 6.52, C.I. 95%: 1.42-30.70 vs controls, and 4.31, C.I. 95%: 0.93-19.82 vs LOAD), after multivariate adjustment. No differences in plasma lipid levels emerged between the three groups after stratification for apo E4 genotype. CONCLUSIONS: In this cross-sectional study low HDL-C levels are associated with VD, but not with LOAD, in a sample of older subjects.
Journal Article↗
Role of diabetes in influencing leptin concentration in elderly overweight patients.
BACKGROUND: Leptin, the product of the ob gene, could have a significant role in the pathogenesis of obesity and non-insulin-dependent diabetes mellitus. However, it is still debated whether different degrees of glucose tolerance may affect plasma leptin concentrations in obese patients. OBJECTIVE: To investigate whether diabetes might influence leptin concentrations in obese patients. METHODS: We evaluated clinical parameters, anthropometric measures, and sex hormones, fasting plasma leptin, glucose and insulin concentrations in 100 elderly obese diabetic patients and 100 obese non-diabetic control individuals matched for age and sex. RESULTS: After adjustment for age and fat mass, plasma leptin concentrations did not differ between diabetic and non-diabetic obese individuals, in both men and women. In all patients leptin was significantly related to body mass index, fat mass and the homeostasis model insulin resistance index; moreover we observed a significant relationship with fasting plasma glucose and age in diabetic obese women, and with blood pressure values and testosterone concentrations in diabetic obese men. Multiple regression analysis revealed age and fasting plasma glucose to be the only independent determinants of fasting plasma leptin in diabetic obese women. CONCLUSIONS: These data suggest that leptin concentrations do not differ between obese diabetic and obese non-diabetic elderly patients. Among correlates of the metabolic syndrome, systolic pressure seems to be related to leptin only in men. In the postmenopausal or andropausal status, sex hormones are related to leptin concentrations only in diabetic men; in diabetic women, however, high glucose seems to be relevant in maintaining the same leptin concentrations as in non-diabetic women with similar degree of obesity.
Age Factors↗
Cystocerebral syndrome: a case report and literature review.
Delirium is a frequent cause of hospitalization in the elderly patient, and can be sustained by several factors, which are not always evident. In 1990 Blackburn and Dunn described a clinical picture characterized by the presence of acute urinary retention presenting as delirium, and named it "cystocerebral syndrome". In 1991 Liem and Carter advanced a possible pathophysiological explanation for this phenomenon, suggesting that adrenergic tension might increase in the central nervous system when micturition cannot occur at the usual threshold. The consequent increase in catecholamines level might produce delirium. We report the case of a very old subject with delirium and acute urinary retention, suggestive of the "cystocerebral syndrome", in order to call the attention of geriatricians to acute urinary retention as a possible precipitating factor of delirium.
Acute Disease↗
White blood cell count is associated with some features of metabolic syndrome in a very old population.
BACKGROUND AND AIMS: Although the association between white blood cell (WBC) counts and the risk of cardiovascular disease has been repeatedly described, its biological mechanism is still unclear. A significant correlation has been demonstrated in adults between WBC counts and some risk factors for coronary heart disease (CHD), including insulin resistance. The aims of this study were: 1) to investigate the association between WBC count and some risk factors for atherosclerosis in a sample of octo-nonagenarians; and 2) to test the hypothesis of an association between WBC count and "metabolic syndrome", a clinical condition mediated by insulin resistance. METHODS AND RESULTS: The study involved 160 free-living healthy octo-nonagenarians participating in the Val Vibrata Aging Project, whose WBC count, and anthropometric and metabolic parameters were measured using standardised methods. WBC count correlated positively with the logarithm of triglyceride, apoprotein B and glucose levels, and negatively with high-density lipoprotein cholesterol: the subjects with low high-density lipoprotein and high triglyceride levels had higher WBC count than normal subjects. The WBC count were significantly higher in the subjects with four or more of six features of metabolic syndrome than in those with three or less. CONCLUSIONS: The results of this study support the existence of a significant association between WBC count and some of the typical features of metabolic syndrome in very old subjects.
Aged↗
Effect of native and oxidized low-density lipoprotein on endothelial nitric oxide and superoxide production : key role of L-arginine availability.
BACKGROUND: Native and oxidized LDLs (n-LDL and ox-LDL) are involved in the atherogenic process and affect endothelium-dependent vascular tone through their interaction with nitric oxide (NO). METHODS AND RESULTS: In this study we evaluated directly, by using a porphyrinic microsensor, the effect of increasing lipoprotein concentrations on endothelial NO and superoxide (O(2)(-)) production. We investigated where lipoproteins may affect the L-arginine-NO pathway by pretreating cells with L-arginine, L-N-arginine methyl ester (L-NAME), and superoxide dismutase. Bovine aortic endothelial cells were exposed for 1 hour to increasing concentrations of n-LDL (from 0 to 240 mg cholesterol/dL) and ox-LDL (from 0 to 140 mg cholesterol/dL). A stimulated (calcium ionophore) NO concentration decreased to 29% of the control at n-LDL concentration of 80 mg cholesterol/dL and to 15% of the control at 20 mg cholesterol/dL of ox-LDL. L-Arginine partially neutralized the inhibitory effect of n-LDL and ox-LDL on the NO generation. Superoxide dismutase pretreatment did not modify NO production, whereas L-NAME blunted NO generation at all LDL concentrations. O(2)(-) production was increased at low n-LDL and very low ox-LDL concentrations; this was reversed by L-arginine. CONCLUSIONS: These findings confirm the inhibitory role of n-LDL and ox-LDL on NO generation and suggest that lipoproteins may induce a decreased uptake of L-arginine. The local depletion of the L-arginine substrate may derange the NO synthase, leading to overproduction of O(2)(-) from oxygen, the other substrate of NO synthase.
Animals↗
The relationship of plasma glucose and electrocardiographic parameters in elderly women with different degrees of glucose tolerance.
Plasma glucose has been regarded as a risk factor for macrovascular complications in diabetes, but less is known about its role in the development of cardiac impairment other than coronary heart disease (CHD). The aim of our study was to determine the relationship between basal and post-OGTT (Oral Glucose Tolerance Test) plasma glucose levels and some ECG parameters in a group of elderly women with normal or impaired glucose tolerance (IGT). One-hundred and one women with normal fasting glucose (<6.0 mmol/L) and no familial history or clinical signs of CHD and diabetes underwent an OGTT and a resting ECG. Based on the degree of glucose tolerance, we identified 24 women with a diagnostic OGTT for either IGT or diabetes; the 77 women (age range 52-88 years) with normal glucose tolerance were further divided into two groups according to their post-OGTT area under the curve (AUCG): below and above the median value (32 and 45 women, respectively). Basal plasma glucose and insulin levels, as well as lipid profile and percent of hypertensive patients were similar in the three groups. Mean corrected QT (QTc) was prolonged as a function of progressive worsening of glucose tolerance even after adjustment for possible confounding factors (p=0.03). A similar relationship was apparent when post-OGTT plasma glucose peak (GP) was considered. In a multiple regression analysis, AUCG and GP were the only factors independently related to both QTc and Sokolow index. Our observations suggest that, even in the presence of a normal glucose tolerance, plasma glucose concentrations during an OGTT are associated with peculiar ECG signs potentially combined with an increased risk of sudden death, arrhythmias, or cardiovascular mortality.
Aged↗
High glucose modulates P2X7 receptor-mediated function in human primary fibroblasts.
AIMS/HYPOTHESIS: Purinergic receptors are a family of newly characterized plasma membrane molecules involved in several and as yet only partially known cellular functions such as vascular reactivity, apoptosis and cytokine secretion. Little is known about the effect extracellular microenvironment has on their function. Fibroblasts share several features with smooth muscle cells and are an important constituent of the atherosclerotic plaque. Our aim was to evaluate the effect of high glucose concentration on ATP-mediated responses in human fibroblasts. METHODS: Fibroblasts were obtained by skin biopsies and grown at two different glucose concentrations. We evaluated receptor expression by RT-PCR and immunoblotting and receptor localization by immunofluorescence. Plasma membrane potential and calcium changes were measured by fluorescent indicators. Apoptosis was determined by ethidium bromide staining and caspase-3 activation. RESULTS: We show that cells grown in a medium with high glucose concentration underwent great ATP-mediated morphological changes, enhanced apoptosis, caspase 3 activation and interleukin-6 release. We identified P2X7 as the main purinergic receptor involved in these responses. Furthermore, high glucose concentration triggered the assembly of P2X7 into ring-like structures located at the periphery of the cells. CONCLUSION/INTERPRETATION: Given that ATP is frequently released into the extracellular milieu upon cell and tissue damage, secretory exocytosis or activation of plasma membrane transporters, we hypothesize that ATP receptors participate in the pathogenesis of vascular complications of diabetes.
Adenosine Triphosphate↗
Benzodiazepines with different half-life and falling in a hospitalized population: The GIFA study. Gruppo Italiano di Farmacovigilanza nell'Anziano.
In recent years, the use of benzodiazepines has been recognized as an independent risk factor for falls among the elderly. To evaluate the role of different types of benzodiazepines in determining falls in a hospitalized geriatric population, we conducted a prospective study among 7908 patients consecutively admitted in 58 clinical centers of the Gruppo Italiano di Farmacovigilanza nell'Anziano (GIFA), during an 8-month observation period (1991 and 1993). Over 70% of the patients were older than 65 years, 50% were women, and 23. 6% had a benzodiazepine prescription during hospital stay. The number of patients who experienced one or more falls during follow-up was 174 (2.2%). Sixty falls occurred among patients taking benzodiazepines (3.2%) and 114 (1.9%) among those who did not use benzodiazepines; the crude odds ratio for users versus non-users was 1.7 (95% CI 1.2-2.3). Multivariate logistic regression analysis showed that benzodiazepines with very short (OR 1.9; CI 1.03-3.3) and short half-life (OR 1.8; CI 1.2-2.8) were positively associated with falls during hospital stay. Patients who used other psychotropic agents (OR 2.3; CI 1.7-3.4), antidiabetic agents (OR 1. 5; CI 1.03-2.2), patients with presence of cognitive impairment (OR 1.6; CI 1.08-2.3), high level of comorbidity (OR 1.7; CI 1.05-2.9), more advanced age (>80 years, OR 2.7; CI 1.5-4.7) and those who stayed in the hospital for 17 days or more (OR 2.1; CI 1.4-3.3) were also at a greater risk. These findings suggest that benzodiazepines with short and very short half-life are an important and independent risk factor for falls and their prescription to elderly hospitalized patients should be carefully evaluated.
Accidental Falls↗
A new locus for autosomal recessive hypercholesterolemia maps to human chromosome 15q25-q26.
High serum cholesterol is an established risk factor for cardiovascular disease and is the prime target for therapeutic intervention in large groups of patients. The development of modern treatments for this major risk factor was propelled by the early realization that forms of severe hypercholesterolemia could be caused by dominantly inherited defects in the LDL receptor or in the APOB gene. Further understanding of the mechanisms contributing to early atherosclerosis will allow for new targets for therapy. We therefore identified and investigated the genetics of families from Sardinia that have recessive inheritance of precocious hypercholesterolemia. We used five families in an analysis of linkage of the autosomal recessive hypercholesterolemia locus, termed "ARH1," to chromosome 15q25-q26. A genomewide search mapped the disease-causing gene with a LOD score of 3.3 and excluded major contributions to the phenotype of other genes. A candidate gene present in the mapped chromosome region-the ligand-activated liver-transcription-factor gene ARP1 (apolipoprotein regulatory-protein gene)-has been excluded after DNA sequencing. The close-bred nature of the Sardinian population offers unique opportunities for isolation of this hypercholesterolemia-causing gene.
Adolescent↗
Reversible hyperthyroidism and cardiomyopathy caused by consumption of iodocasein.
We report the case of a 52-year-old woman with recent diagnosis of acute myocarditis and pericarditis, admitted for fever, tachycardia, and dyspnea upon exertion. Hematochemical parameters and instrumental examinations suggested iatrogenic hyperthyroidism and secondary dilated cardiomyopathy. Although gathering information about the medication used at home was initially difficult because of the patient's refusal to cooperate, she ended up by disclosing the regular assumption of an iodocasein drug. A complete and stable regression of the clinical picture was reached by suspending the iodine derivative and using cardiovascular drugs.
Cardiomyopathy, Dilated↗
Detection of nitric oxide release induced by bradykinin in guinea pig trachea and main bronchi using a porphyrinic microsensor.
Indirect evidence using nitric oxide (NO) synthase (NOS) inhibitors suggests that in guinea-pig airways bradykinin releases bronchoprotective NO. In this study, using a recently developed electrochemical method of NO measurement based on a porphyrinic microsensor, we investigated whether bradykinin releases NO from guinea-pig airways and whether the epithelium is the main source of NO. Further, the Ca(2+)-dependence of bradykinin-induced NO release was assessed stimulating airway preparations with bradykinin in Ca(2+)-free conditions. We also studied the immunohistochemical distribution of the Ca(2+)- dependent constitutive isoforms of NOS (constitutive NOS [cNOS]: neuronal and endothelial [ecNOS]) in our preparations. The porphyrinic microsensor was placed in the bathing fluid onto the mucosal surface of tracheal or main bronchial segments. Addition of bradykinin vehicle (0.9% saline) did not cause any detectable change of the baseline signal. Addition of bradykinin caused an upward shift of the baseline that reached a maximum within 1 to 2 s. The amplitude of the response to bradykinin was concentration-dependent between the range 1 nM to 10 microM, with a maximum effect at 10 microM. Bradykinin-induced NO release was higher in tracheal than in main bronchial segments. The selective bradykinin B(2) receptor antagonist D-Arg(0)-[Hyp(3), Thi(5), D-Tic(7), Oic(8)]bradykinin (1 microM) inhibited NO release induced by a submaximum concentration of bradykinin (1 microM). The ability of bradykinin to release NO was markedly reduced in epithelium-denuded segments, and abolished in Ca(2+)-free conditions and after pretreatment with N(G)-monomethyl-L-arginine (100 microM), but not with N(G)-monomethyl-D-arginine. Both cNOS isoforms were present in trachea and main bronchi, ecNOS being the predominant isoform in the epithelium. The study shows that bradykinin via B(2) receptor activation caused a rapid and Ca(2+)-dependent release of NO, mainly, but not exclusively, derived from the epithelium. It also shows that both cNOS isoforms may be involved in bradykinin-evoked NO release.
Animals↗
Factors influencing plasma homocysteine levels in type 2 diabetes.
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Albuminuria↗
Plasma lipoproteins in soy-treated postmenopausal women: a double-blind, placebo-controlled trial.
BACKGROUND AND AIM: Postmenopausal modification of the lipid profile plays a major role in the risk of ischemic heart disease. Lifestyle counseling and estrogen replacement therapy have all been proposed as first-line measures, but there is no agreement on the best way to treat climacteric dyslipidemia. Soybean-based diet seems particularly attractive in this context, given its cholesterol lowering potential, its hypothetical anticancerous effects and possible modification of climacteric symptoms. METHODS AND RESULTS: We evaluated the effect of 60 g isolated soy protein (ISP) daily on the lipid profile of 104 postmenopausal women (53.3 +/- 3.3 years) in a double-blind, parallel, placebo-controlled (caseinate) trial, as part of a broader assessment of the effect of ISP on climacteric symptomatology. Serum total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, apo A-I, apo B and lipoprotein (a) were determined before and after a 12-week diet modification. Seventy-seven women completed the trial. Both soy and placebo determined a significant reduction in total cholesterol (-0.42 +/- 0.79 and -0.40 +/- 0.57 mmol/L) and LDL-cholesterol (-0.35 +/- 0.72 and -0.31 +/- 0.54 mmol/L), but only soy had a significant lowering effect on apo B and the LDL-cholesterol/HDL-cholesterol ratio (-6% and -8% from baseline respectively); lipoprotein (a) plasma levels were not significantly changed by either treatment. Forty-four women were dyslipidemic at baseline; those with increased LDL concentrations showed a somewhat greater improvement in their lipoprotein profile (LDL-cholesterol and apo B reduction) with soy rather than placebo. No further information emerged when the subjects were divided into three apo E phenotypes. CONCLUSIONS: We conclude that diet supplementation with 60 g ISP is slightly better than caseinate in favorably modifying the lipoprotein metabolism of postmenopausal women; this effect is more evident in hypercholesterolemic subjects.
Caseins↗
Circulating thyroid autoantibodies in a sample of Italian octo-nonagenarians: relationship to age, sex, disability, and lipid profile.
Circulating thyroid autoantibodies were assessed in a sample of Italian octo-nonagenarians living in a restricted area (Val Vibrata, Abruzzo), and selected according to the absence or presence of chronic illness and disability. The study groups included: Group A ("Successful aging"), 98 free-living healthy, fully independent, octo-nonagenarians (57 males and 41 females, average age +/-SD 83.9+/-3 years); Group B ("Unsuccessful aging"), 62 highly disabled octo-nonagenarians (24 males and 38 females; average age 86.5+/-3.4 years), and Group C (Controls), 91 randomly selected healthy adult controls (42 males and 49 females; age 53.7+/-16.6 SD years, range 20-70). Serum autoantibodies to thyroglobulin (anti-Tg) and to thyroid peroxidase (anti-TPO) were measured by passive hemagglutination and radioimmunoassays (RIA); serum free thyroxine and thyrotropin by RIA. The prevalence of positive thyroid autoantibody tests was not significantly increased in the elderly groups compared to the controls, with the remarkable exception of anti-Tg detected by RIA which were increased in disabled elderly, compared to free-living elderly and controls. Two/62 disabled elderly had subclinical (1) or mild (1) primary hypothyroidism, and one free-living woman aged 90 years was hyperthyroid (toxic nodular goiter). No correlation was found between serum thyroid autoantibodies, thyroid hormones and TSH and serum lipoprotein fractions. The higher prevalence of thyroid autoantibodies found only in disabled, but not in free-living Italian octo-nonagenarians suggests that thyroid autoimmune phenomena in the elderly may be an expression of age-associated disease rather than related to the aging process in itself.
Aged↗